Metabolism of 7,12-dimethylbenz(a)anthracene and 7-hydroxymethyl-12-methylbenz(a)anthracene by rat liver and microsomes.
The metabolism of 7,12-[14C]dimethylbenz(a)anthracene ([14C]DMBA) and 7-[7-CH2-3H]hydroxymethyl-12-methylbenz(a)anthracene ([7-CH2-3H]7-OHM-12-BMA) by rat liver nuclei and microsomes was studied by high-performance liquid chromatography. DMBA and 7-OHM-12-MBA are metabolized at methyl group(s) and at the aromatic ring carbons to form trans-dihyrodiols at positions 3, 4, 5, 6, 8, 9, and 10,11 and phenols at positions 2, 3, and 4 by both nuclear and microsomal enzymes. Both nuclear and microsomal monooxygenase enzyme activities were inducible by pretreatment of the animals with phenobarbital or 3-methylcholanthrene. The rates of formation of all metabolites by microsomes were five- to 20-fold higher than those by nuclei in metabolizing DMBA or 7-OHM-12-MBA. The presence of a hydroxyl group at the 7-methyl position of DMBA markedly decreased the rate of metabolism. The rate of total metabolism of 7-OHM-12-MBA was only 20 to 70% of that of DMBA under identical in vitro incubation conditions. The 3-methylcholanthrene- and phenobarbital-induced enzymes showed a significantly different regioselectivity toward the metabolism of DMBA or 7-OHM-12-MBA and are attributed to different forms of cytochrome P-450 present in the enzyme preparations.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D002273:Carcinogens; D002467:Cell Nucleus / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D008748:Methylcholanthrene; C018970:7-hydroxymethyl-12-methylbenz(a)anthracene; D015127:9,10-Dimethyl-1,2-benzanthracene; D010634:Phenobarbital